Overview

Andres Buonanno, who heads the Section on Molecular Neurobiology, and his colleagues focus on the Neuregulin (NRG) ErbB signaling pathway. Importantly, genes encoding the neurotrophic factors NRG-1 and NRG-3, as well as their receptor ErbB4, were identified as "at risk" genes for schizophrenia and other psychiatric disorders. Using a combination of molecular, cellular, electrophysiological, and behavioral approaches, the SMN found that (i) NRG-1 reverses long-term potentiation at glutamatergic synapses via a novel signaling pathway linking activation of ErbB4 to dopamine release, and (ii) downstream activation of D4 dopamine receptors triggers the rapid internalization of surface glutamate receptors. In collaborative studies, the SMN also showed that NRG-1 signaling modulates gamma oscillatory network activity and that such activity requires ErbB4 receptors expressed in fast-spiking interneurons. The functional link between NRG-1/ErbB4 signaling with glutamatergic transmission and D4 dopamine receptors (a target for clozapine and other antipsychotics), along with its link through GABAergic neurons to modulate gamma oscillation power (reduced in schizophrenia patients), begins to uncover pathways that are genetically, pharmacologically, and functionally implicated in cognitive functions and psychiatric disorders.